Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis--a longitudinal study

PLoS One. 2013 Apr 25;8(4):e62885. doi: 10.1371/journal.pone.0062885. Print 2013.

Abstract

Background: The human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH). The relationship between microbiota changes and changes in hepatic steatosis was also studied.

Methods: Fecal microbiota of histology-proven NASH patients and healthy controls was analyzed by 16S ribosomal RNA pyrosequencing. NASH patients were from a previously reported randomized trial on probiotic treatment. Proton-magnetic resonance spectroscopy was performed to monitor changes in intrahepatic triglyceride content (IHTG).

Results: A total of 420,344 16S sequences with acceptable quality were obtained from 16 NASH patients and 22 controls. NASH patients had lower fecal abundance of Faecalibacterium and Anaerosporobacter but higher abundance of Parabacteroides and Allisonella. Partial least-square discriminant analysis yielded a model of 10 genera that discriminated NASH patients from controls. At month 6, 6 of 7 patients in the probiotic group and 4 of 9 patients in the usual care group had improvement in IHTG (P=0.15). Improvement in IHTG was associated with a reduction in the abundance of Firmicutes (R(2)=0.4820, P=0.0028) and increase in Bacteroidetes (R(2)=0.4366, P=0.0053). This was accompanied by corresponding changes at the class, order and genus levels. In contrast, bacterial biodiversity did not differ between NASH patients and controls, and did not change with probiotic treatment.

Conclusions: NASH patients have fecal dysbiosis, and changes in microbiota correlate with improvement in hepatic steatosis. Further studies are required to investigate the mechanism underlying the interaction between gut microbes and the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Case-Control Studies
  • Fatty Liver / microbiology*
  • Feces / microbiology*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Microbiota*
  • Middle Aged
  • Phylogeny
  • Young Adult

Grants and funding

The work described in this paper was partially supported by the Direct Grant of The Chinese University of Hong Kong (Reference no. 2010.1.042). The additional part of the funding of our study came from the authors’ own team. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.